Objective Dopamine signaling is one of the major pathways of modulatory neurotransmission in the brain. Dysfunctions of the dopaminergic system are involved in several neurological and psychiatric disorders. Investigation of the function of the different dopamine receptors will shed further light on the role of dopaminergic neurotransmission in the brain and increase our understanding of the pathogenic mechanisms involved in dopamine-related disorders. Previous work by the host laboratory has indicated that mice with targeted inactivation of the dopamine D2 receptor (D2R) exhibit higher degree of epileptic seizures and increased neuronal cell death when treated with glutamatergic or cholinergic agonists. These results and recent work by other laboratories that has suggested the implication of D2R in neuronal degeneration in Parkinson and apos;s disease have raised the question of what are the molecular mechanisms that underlie control of neuronal survival by D2R. The proposed project aims to address this question by the use of existing and novel genetically modified mouse models and of a cell culture system. The mouse lines that will be used are D2R-deficient mice and mice lacking either one of the two alternatively spliced D2R isoforms. Neuronal cell death induced by epileptogenic agents or by a parkinsonism-causing neurotoxin will be examined in mutant and control mice by morphological and stereological methods and the degree of epileptic and parkinsonian phenotypes will be assessed by behavioural testing. Alterations in potentially underlying molecular pathways will be studied by biochemical and gene expression analyses. To investigate what changes in cellular physiology may be associated with neuronal loss mediated by D2R dysfunction, a system of cultured primary striatal neurons will be used, as well as electrophysiological measurements, performed in collaboration, using mouse brain slices. Fields of science medical and health sciencesbasic medicineneurologyepilepsymedical and health sciencesclinical medicinepsychiatrymedical and health sciencesbasic medicinephysiologymedical and health sciencesbasic medicineneurologyparkinson Keywords Dopamine Receptor Genetics Knockout mice Inducible Cell culture Striatum Neurodegeneration Molecular pathways Epilepsy Seizure Parkinson’s disease Substantia nigra Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2004-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE - GROUPEMENT INTERET ECONOMIQUE EU contribution No data Address 1 rue Laurent Fries 10142 Illkirch France See on map Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
